The purpose of this study is to evaluate if ibrutinib administered in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the clinical outcome in newly diagnosed patients with non-germinal center B-cell subtype (GCB) of diffuse large B-cell lymphoma (DLBCL).

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:

Event-free survival [ Time Frame: Up to disease progression, relapse from complete response, initiation of subsequent systemic antilymphoma therapy after completion of at least 6 cycles of R-CHOP therapy, or death, whichever occurs first, up to Year 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Time Frame: Up to disease progression, relapse from complete response, or death, whichever occurs first, up to Year 7 ] [ Designated as safety issue: No ]

Overall survival [ Time Frame: Up to the date of the participants death, up to Year 7 ] [ Designated as safety issue: No ]

Complete response rate [ Time Frame: Up to completion of chemotherapy treatment, up to Year 7 ] [ Designated as safety issue: No ]

Time to worsening symptoms in the Lym subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) [ Time Frame: Up to the start date of the worsening of patient symptoms, up to Year 7 ] [ Designated as safety issue: No ]

375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Cyclophosphamide

750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Doxorubicin

50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Vincristine

1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Prednisone (or equivalent)

100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle

Experimental: Treatment Arm B: ibrutinib + R-CHOP

Treatment Arm B = ibrutinib + R-CHOP

Drug: Ibrutinib

560 mg capsules administered by mouth once daily (21-day cycles)

Drug: Rituximab

375 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Cyclophosphamide

750 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Doxorubicin

50 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Vincristine

1.4 mg/m2 administered intravenously once on Day 1 of each cycle (21-day cycles)

Drug: Prednisone (or equivalent)

100 mg capsules administered by mouth once daily on Day 1 to Day 5 of each cycle

Detailed Description:

This is a randomized (individuals assigned to study treatment by chance), double-blind (individuals and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to compare the efficacy and safety of ibrutinib in combination with R-CHOP versus R-CHOP alone in adult patients newly diagnosed non-GCB DLBCL. The study will include screening, active treatment, and posttreatment follow-up phases. The study will end when 50% of participants have died or the sponsor terminates the study, whichever occurs first (up to approximately 7 years). Approximately 800 participants will be randomly assigned in a 1:1 ratio to receive either placebo+R-CHOP (treatment arm A) or ibrutinib+R-CHOP (treatment arm B). All participants will receive R-CHOP as background therapy for 6 or 8 cycles (21 days per cycle) prespecified according to local practice. After 4 treatment cycles, an interim response assessment will be performed to evaluate disease progression for each participant. Participants with progressive disease or relapsed disease after complete response will be discontinued from treatment. Participants who discontinue R-CHOP without disease progression will continue study drug (placebo or ibrutinib) until 6 or 8 cycles are completed, disease progression, or unacceptable toxicity, whichever occurs first. After completion of study drug, participants will undergo assessment of tumor response based on the Revised Response Criteria for Malignant Lymphoma. Participants with documented residual disease upon completion of at least 6 cycles of R-CHOP therapy are considered eligible to initiate subsequent antilymphoma therapy. Serial pharmacokinetic samples will be collected before and after dosing, and safety will be monitored throughout the study.

Agrees to protocol-defined use of effective contraception (for women, these restrictions apply for 12 months after the last dose of rituximab or 1 month after the last dose of study drug, whichever is later; for men, these restrictions apply for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later)

Men must agree to not donate sperm during and after the study for 12 months after the last dose of rituximab or 3 months after the last dose of study drug, whichever is later

Women of childbearing potential must have a negative serum or urine pregnancy test at screening

Exclusion Criteria:

Major surgery within 4 weeks of random assignment

Known central nervous system or primary mediastinal lymphoma

Prior history of indolent lymphoma

Diagnosed or treated for malignancy other than DLBCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before random assignment; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease

History of stroke or intracranial hemorrhage within 6 months prior to random assignment

Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification

Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01855750

Contacts

Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: